The concept of the lower esophageal sphincter (LES) as one of the major barriers to gastroesophageal reflux is well established. It has also been established that LESP increases in response to a protein meal (1,10). This increase resembles in many ways the sphincteric response to infusion of acid into the cardia of the stomach and some have proposed that the postprandial increase in lower esophageal sphincter pressure is a protective response of the sphincter to acid (10,15). Recent studies from our laboratory (44) have established that exclusion of the duodenum from contact with gastric chyme abolishes the postprandial increase in LESP and that this phenomenon is accompanied by a corresponding decrease in postprandial pancreatic polypeptide, a hormone known to stimulate LESP (38). Others have shown that infusion of peptones into an excluded duodenum results in an increase in lower esophageal sphincter pressure similar to that seen following feeding (18). The hypothesis that the postprandial increase in lower esophageal sphincter pressure is a protective response of the sphincter to bathing of the cardiac aspect of the stomach with acid will be tested in two major groups of experiments. These experiments will dissect in detail the neurohormonal mechanisms involved in the response of the sphincter to 1) acid and 2) food by utilizing pharmacologic manipulations and selective cholinergic or adrenergic denervation. The third group of experiments will attempt to define the role of the duodenum. This group of experiments will study the effects of somatostatin induced suppression of enteral hormone release, selective vagal denervation, and physiologic infusion of gastrointestinal hormone on the response of the LES to intraduodenal infusion of peptone, to determine the role of the duodenum, if any, in the genesis of postprandial increases in LESP. A fourth series of experiments has been designed to evaluate the role of postprandial increases in LESP on maintenance of gastroesophageal competence. This last group of experiments utilizes continuous pH monitoring, both before and after the operative procedure of duodenal exclusion (which abolishes the postprandial increase in lower esophageal sphincter pressure) to determine the physiologic contribution of postprandial sphincter pressure to gastroesophageal competence. A fifth group of experiments explores the role of pancreatic polypeptide in the genesis of postprandial increases in LESP in humans and studies the effect of eliminating this increase in sphincter pressure on competence.